STEREOCHEMISTRY - chem.uky. · PDF filePrinciples of Organic Chemistry lecture 10, page 1...
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Principles of Organic Chemistry lecture 10, page 1 STEREOCHEMISTRY • Dissymmetric versus asymmetric. o Asymmetric: lacking symmetry, C 1 point group. o Dissymmetric: lacking some particular symmetry element. This term might be used with respect to the particular symmetry element. One might say the object is dissymmetric with respect to a σ v . o All objects/ molecules that are asymmetric are chiral. o All objects/ molecules that are dissymmetric with respect to Sn are chiral. The chiral point groups are C 1 (asymmetric), C n , and D n (dissymmetric). H H H H H H C 3 C 2 C 2 C 2 • D 3 no mirrors, no improper rotations. • This molecule is chiral. • At this point the instructor plays with a flexible cube to demonstrate this the ideas above. • Some Stereochemistry verbiage: I will discuss the following terms and what they mean. The table below was copied from C&EN 1984, June 11, p. 21. and the ideas of Prof. Kurt Mislow. Br chirotopic achirotopic stereogenic nonstereogenic Cl H F Br Cl H H OH H CO 2 H CO 2 H HO HO H H OH H CO 2 H CO 2 H HO HO H H o The absolute configuration of the product is just a name! It depended in this case on the priority (nomenclature, not chemistry) of the nucleophile. Names are arbitrary. o Review the Cahn, Ingold Prelog rules in an Organic Chemistry Textbook if you think this is necessary.
Transcript of STEREOCHEMISTRY - chem.uky. · PDF filePrinciples of Organic Chemistry lecture 10, page 1...
Principles of Organic Chemistry lecture 10, page 1
STEREOCHEMISTRY • Dissymmetric versus asymmetric.
o Asymmetric: lacking symmetry, C1 point group.
o Dissymmetric: lacking some particular symmetry element. This term might be used with respect to the particular symmetry element. One might say the object is dissymmetric with respect to a σv.
o All objects/ molecules that are asymmetric are chiral.
o All objects/ molecules that are dissymmetric with respect to Sn are chiral.
The chiral point groups are C1 (asymmetric), Cn, and Dn (dissymmetric).
H
H
H
H
H
HC3
C2
C2
C2
• D3 no mirrors, no improper rotations.
• This molecule is chiral.
• At this point the instructor plays with a flexible cube to demonstrate this the ideas above.
• Some Stereochemistry verbiage:
I will discuss the following terms and what they mean.
The table below was copied from C&EN 1984, June 11, p. 21. and the ideas of
Prof. Kurt Mislow.
Br
chirotopic achirotopic
stereogenic
nonstereogenic
Cl
H F
BrCl
H H
OH
H
CO2H
CO2H
HO
HOH
H
OH
H
CO2H
CO2H
HO
HOH
H
o The absolute configuration of the product is just a name! It depended in this case on the
priority (nomenclature, not chemistry) of the nucleophile.
Names are arbitrary.
o Review the Cahn, Ingold Prelog rules in an Organic Chemistry Textbook if you think this
is necessary.
Principles of Organic Chemistry lecture 10, page 2
http://www.vanderbilt.edu/AnS/Chemistry/Rizzo/chem220a/absolute.pdf
• Other designators
o axial versus point chirality:
2,3-pentadiene has axial chirality
R,S designation can be applied, but it is not so convenient.
• Instructor demonstrates.
The simplest axial chirality can be found in a helix or a spiral.
• identical ends
• What is the point group of a simple helix?
o Only symmetric with respect to C2 so C2.
o Right handed helix . . . use the right hand rule along the dissymmetric axis. Why dissymmetric and not asymmetric here?
Instructor demonstrates with a helix drawn on the board.
Instructor demonstrates with 2,3-pentadiene on the board.
o Instructor talks about molecules in terms of M versus P designations
M = Left handed helix.
P = Right handed helix.
o enantiomers:
These molecules can be designated (1S,2S) and (1R,2R) respectively. Remember the way we proceeded for a molecule devoid of stereogenic atoms?
• We made an analogy between the helix and the structure.
•
HC
H
H
CH3
CH3C H
H
CH3
CH3C H
o a left-handed helix so apply the M designation. o the steps are
1) find the axis perpendicular to the axis of symmetry (the C2 in this case)
2) Apply Kahn-Ingold-Prelog rules in nomenclature to determine the handedness.
Go from highest priority group to highest priority group along the axis of dissymmetry.
Did this progression follow a left or aright handed helix? If left then m, if right then p.
Principles of Organic Chemistry lecture 10, page 3
• The major difference between diastereomers and enantiomers is (drum role, please):
o Enantiomers have identical properties; diastereomers have non-identical properties.
Worded colloquially: energy diagrams have identical mirror images.
o There are no exceptions to this rule.
• Parity conservation
o C.S.Wu, and C.N.Yang Nobel Prize: 1957
Parity of beta emission is not conserved
Instructor explains.
Our universe is chrial!
• Is this a violation of the rule?
o No
o If you compare enantiomer R in our universe to enantiomer S in an antimatter universe they would be exactly at the same energy.
o Before the big bang there is parity. Bang! There ensues a process in which matter and antimatter destroy each other. Matter wins and parity is no longer conserved.
The difference between R and S enantiomers in our universe is about 1E−18 kcal/mol.
H3C H
O
H3C H
O o The above process is racemization and involves the conversion of one enantiomer into
another. Enantiomers can racemize. After they do we call the mixture optically impure or
racemic.
The two structures above are enantiomers of each other.
H3C H
O
OHCH3
O
O
o The above process is epimerization and involves the conversion of one diastereomer into
another. Diastereomers can epimerize.
The two structures above are diastereomers of each other.
• Diastereomers that only differ by one stereogenic atom are referred to as
epimers.
Instructor draws energy diagrams
o
HCH3
O
O H3CH
O
O
Principles of Organic Chemistry lecture 10, page 4
• What is going on in the following scenario?
o A racemic mixture of trans-1,2-diaminocyclohexane is treated with 1 equivalent
(l+)-tartaric acid (R,R). A salt forms that contains only R,R-diamine and R,R-tartaric acid.
- one of the diastereomeric pairs of salts has less solubility than the other
- this can occur because diatereomers have different physical and chemical properties
HO2CCO2H
OH
OH
NH2
NH2
NH2
NH2
HO
CO2(-)
CO2(-)
HO H3N
H3N
o DISCUSSION FOLLOWS involving holding hands, cricket, baseball and beauty:
• Discussion about the handedness of light.
o draw diagrams to describe light.
white light
polarized light
• Consists of two chirotopic components
o l and r
o A discussion on how to polarize light can be found at:
http://hyperphysics.phy-astr.gsu.edu/hbase/phyopt/polar.html#c1
o A molecule with two stereogenic centers produces a pair of diastereomers
• One enantiomer plus polarized light produces two diastereomeric pairs.
o Dissymmetric elements (elements here do not necessarily refer to atoms) do not have to be physically connected.
o After all nothing is really physically connected.
• Rotation of polarized light
o ORD
optical rotatory dispersion:
• optical rotation as a function of wavelength.
o Optical Rotation
o When measuring optical rotation you want to hit it all you have, monochromatic light.
differences in the index of refraction
• speed of light through the medium.
• n = C/v
• ∆n = nR − nL.
o CD (circular dichroism).
• low intensity
o you want to accentuate absorption differences
Principles of Organic Chemistry lecture 10, page 5
differences in absorption of l and R.
• A = εCL Beer law.
• ∆A = εRCL – εLCL
• ∆A = ∆εCL
o Beer’s law holds for CD.
• Symmetry as it relates to substituents
o the chemical dichotomy between diastereomers vs. enantiomers is a powerful guide to what to expect regarding physical properties and reaction mechanisms.
o there is a similar list of descriptors to decide how two (or more) substituents in a molecule are related
homotopic, enantiotopic, diastereotopic, heterotopic
o Method to differentiate between the four:
1) substitute the atoms in question with X thereby giving two (or) structures.
2) determine how these structures are related.
-) if the two structures are identical ->> the two substituents are homotopic
-) if the two structures are enantiomers ->> the two substituents are enantiotopic
-) if the two structures are diastereomers ->> the two substituents are diastereotopic
-) if the two structures are constitutional isomers ->> the two substituents are heterotopic
o What does this all mean? Why does the chemist care to categorize substituents in this manner?
Homotopic and enantiotopic substituents have identical reactivity with achiral reagents.
Likewise contributions to any spectral signal are identical.
Enantiotopic substituents will differ in reactivity when the molecule interacts with (catalyst, reagent, chelator, etc) a chiral molecule.
• Why?
Diastereomeric substituents will have different reactivities with all reagents whether the reagent is chiral or not. The same can be said for their spectral signals.
• Since the connections of these substituents must be related these reactivities and spectral signals are often similar.
Heterotopic substituents are different period.
• Let’s do some examples!
Principles of Organic Chemistry lecture 10, page 6
X
X
X
X
A B
C D
X
XE F
XG H
X
W
X
Y
Z
o In W the two methyl groups are homotopic.
Substitution produces A and B which give rise to identical molecules.
It should be rather intuitive that these groups are homotopic.
When the molecule tumbles on the C2 axis the methyl groups transform.
o In molecule X the two methyl groups are enantiotopic.
Upon substitution the enantiomers are obtained.
The symmetry element that relates these two groups is improper.
• a reflection
• the two groups do not transform when the molecule tumbles.
• Substitution of methyl with X breaks the σv symmetry.
OHON O
N O
OO
+H
+ON
OOH
• Molecules / energy / isomers /
o In molecule X the two methyl groups are enantiotopic.
Upon substitution the enantiomers are obtained.
The symmetry element that relates these two groups is improper.
• a reflection
Principles of Organic Chemistry lecture 10, page 7
• the two groups do not transform when the molecule tumbles.
OHON O
N O
OO
+H
+ON
OOH
• 1,3-cyclohexane dicarboxaldehyde should react with the proline-derived base at different rates.
• likewise the two products shown should have different energies.
o N OH
H
Let’s talk about what the 1H NMR signals of the hydrogen atom might look like.
• Class discussion evolves
o W and Z interconvert.
The conformers are enantiomers.
The substitution products before conformations change are diastereomers.
• Thus, Diastereotopic
Since the conformers interconvert, dynamically the substitution points are enantiotopic.
• Y is not chiral.
